Candidate pharmaceutical and cosmetic compounds and formulations are generally tested for diffusion across skin. Most preferably, excised human cadaver skin or human skin left over from cosmetic surgery is used for such testing, typically in an in-vitro experimental set up. Although not ideal, excised animal skin is also sometimes used for investigating transdermal diffusion of various compounds and formulations, e.g., skin from rat, mouse or pig. However, results obtained with excised animal skin and animal models cannot always be extrapolated to human skin. Further, obtaining enough supply of excised human and animal skin is often a challenge and tends to be costly.
Furthermore, there are bioengineered skin equivalents such as Grallskin™ LSE which are also available for the transdermal diffusion testing of candidate formulations and compounds. However, such equivalents are often costly and have been shown to not be suitable for the testing of all compounds, as they often show a much higher diffusion rate for various compounds than human skin. See, Schmook et al., Int J. Pharm. 215:51-56 (2001).
Lastly, in addition to excised human and animal skin and bioengineered skin equivalents, there have been attempts to create synthetic membranes which may be used as human skin models to investigate transdermal diffusion properties of pharmaceutical and cosmetic compounds and formulations. These include membranes such as low-density polyethylene (LDPE) membrane, cellulose acetate membrane, silicone membrane, hydrophobic polyvinylidene fluoride (PVDF) membrane, polycarbonate membrane, chitosan membrane, composite cellophane membrane, poly (dimethylsiloxane) membrane and cellulose nitrate membrane, with various modifications. See, e.g., Wang et al., Int. J. Pharm., 310:110-117 (2006); Dias et al., Int. J. Pharm., 182:41-47 (1999); Leveque et al. Int. J. Pharm., 318:49-54 (2006); Ottaviani et al., J. Med. Chem., 49: 3948-3954 (2006); Ottaviani et al., J. Med. Chem., 50:742-748 (2007); Leveque et al., Int. J. Pharm., 269: 323-328 (2004); Dureja et al., ltd. Pharm., 213:193-198 (2001); Loftsson et al., Int. J. Pharm., 326:60-68 (2006); Frum et al., Eur. J. Pharm. Biopharm., 67: 434-439 (2007); and Mura et al., Eur. J. Pharm. Biopharm., 67:86-95 (2007).
However, none of the existing synthetic membranes provide a suitable skin substitute for investigating transdermal diffusion properties of a wide range of pharmaceutical and cosmetic compounds and formulations because of low reproducibility and/or high variability compared to human skin.